Patients with AIDS have repeated episodes of severe systemic infection associated with marked abnormalities in immune function. Perhaps the principle system for clearing the bloodstream of infection is termed the reticuloendothelial or mononuclear phagocyte system. In general, in systemic infections, this system shows enhanced capacity to clear the bloodstream of foreign substances. We have instituted a prospective study to exmaine alterations in RES function in homosexual men with acute self-limited viral infections, lymphadenopathy and AIDS. RES activity in patients is assessed by measuring Fc and C3b receptor functions via clearance kinetics of IgG and IgM sensitized 51Cr-labeled erythrocytes. These studies will be performed serially on each patient and correlated with disease progression, immune complexes, RES blood flow kinetics, plasmaphoresis, and other immunologic alterations such as T cell responsiveness, subsets and Fc C3b receptors on circulating monocytes. In preliminary studies we have examined two AIDS patients with Kaposi's sarcoma, six AIDS patients with opportunistic infections, three lymphadenopathy patients (one on plasmaphoresis) and three "healthy" homosexual men. All but one of the "control" homosexual patients had elevated immune complexes (40-60% C1q binding assay). All the AIDS patients had prolonged clearance of IgG-sensitized RBCs (mean t-1/2 98 min, slope 0.007) compared to normal or slightly accelerated clearance rates in the lymphadenopathy patients and controls (mean t-1/2 28 min, slope 0.02). Two of the AIDS patients demonstrated prolongation of clearance rates with further deterioration in their clinical status suggesting further alteration in RES function. Similar results were found in a patient with Kaposi's sarcoma receiving interferon. These patients and others will be studied to assess alterations of RES function in relation to further disease progression, response to therapy and whether RES dysfunction predates the first opportunistic infection.